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Profile Name | IDH1 R132C |
Gene Variant Detail | |
Relevant Treatment Approaches | IDH Inhibitor (Pan) IDH1 Inhibitor |
Molecular Profile | Indication/Tumor Type | Response Type | Relevant Treatment Approaches | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|---|
IDH1 R132C | sarcoma | sensitive | Olaparib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Lynparza (olaparib) treatment delayed tumor growth in cell line xenograft models of sarcoma harboring IDH1 R132C (PMID: 28148839). | 28148839 | |
IDH1 R132C | fibrosarcoma | sensitive | Ceralasertib + Olaparib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, the combination of Lynparza (olaparib) and Ceralasertib (AZD6738) resulted in a greater delay in tumor growth compared to Ceralasertib (AZD6738) alone in fibrosarcoma cell line xenograft models harboring IDH1 R132C (PMID: 34027408). | 34027408 | |
IDH1 R132C | sarcoma | decreased response | IDH1 Inhibitor | AGI-5198 + Talazoparib | Preclinical - Cell culture | Actionable | In a preclinical study, AGI-5198 reverted the sensitivity of sarcoma cells harboring IDH1 R132C to Talazoparib (BMN-673)-induced growth inhibition in culture (PMID: 28148839). | 28148839 |
IDH1 R132C | fibrosarcoma | predicted - sensitive | IDH Inhibitor (Pan) | AG-881 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, AG-881 treatment decreased tumor 2HG levels in a fibrosarcoma cell line xenograft model harboring IDH1 R132C (Mol Cancer Ther Jan 1 2018 (17) (1 Supp) B126). | detail... |
IDH1 R132C | high grade glioma | sensitive | Talazoparib | Preclinical - Patient cell culture | Actionable | In a preclinical study, patient-derived glioma cells harboring IDH1 R132C demonstrated increased sensitivity to Talazoparib (BMN-673)-induced growth inhibition in culture (PMID: 28148839). | 28148839 | |
IDH1 R132C | Advanced Solid Tumor | predicted - sensitive | IDH1 Inhibitor | DS-1001b | Preclinical - Cell culture | Actionable | In a preclinical study, DS-1001b inhibited IDH1 R132C enzymatic activity in an in vitro assay, and inhibited production of the oncometabolite 2-hydroxyglutarate (2-HG) in transformed human cells expressing IDH1 R132C in culture (PMID: 31727689). | 31727689 |
IDH1 R132C | sarcoma | decreased response | IDH1 Inhibitor | AGI-5198 + Olaparib | Preclinical - Cell culture | Actionable | In a preclinical study, AGI-5198 reverted the sensitivity of sarcoma cells harboring IDH1 R132C to Lynparza (olaparib)-induced growth inhibition in culture (PMID: 28148839). | 28148839 |
IDH1 R132C | intrahepatic cholangiocarcinoma | sensitive | Saracatinib | Preclinical | Actionable | In a preclinical study, intrahepatic cholangiocarcinoma cells harboring IDH1 R132C demonstrated increased sensitivity to Saracatinib (AZD0530) induced growth inhibition compared to IDH1 wild-type cells in culture (PMID: 27231123). | 27231123 | |
IDH1 R132C | chondrosarcoma | predicted - sensitive | Olaparib | Case Reports/Case Series | Actionable | In a Phase II trial (OLAPCO), Lynparza (olaparib) treatment resulted in a partial response with 59% tumor reduction lasting 14 months in one patient and stable disease lasting 7.5 months in one patient out of four patients with chondrosarcoma harboring IDH1 R132C (PMID: 34994649, NCT02576444). | 34994649 | |
IDH1 R132C | acute myeloid leukemia | sensitive | IDH1 Inhibitor | Ivosidenib | FDA approved - On Companion Diagnostic | Actionable | In a Phase I trial that supported FDA approval, Tibsovo (ivosidenib) treatment resulted in complete remission (CR) in 21.6% (27/125), CR with partial hematological recovery (CRh) in 8.8% (11/125), and overall response (OR) in 41.6% (52/125) of patients with relapsed or refractory acute myeloid leukemia harboring a susceptible IDH1 mutation (R132C/G/H/L/S) as detected by an FDA-approved test (PMID: 29860938; NCT02074839). | detail... detail... detail... 29860938 |
IDH1 R132C | acute myeloid leukemia | sensitive | IDH1 Inhibitor | Ivosidenib | FDA approved - On Companion Diagnostic | Actionable | In a Phase I trial that supported FDA approval, Tibsovo (ivosidenib) treatment resulted in complete remission (CR) in 28.6% (8/28), CR with partial hematological recovery (CRh) in 14.3% (4/28) of patients age 75 or older with untreated acute myeloid leukemia harboring a susceptible IDH1 mutation (R132C/G/H/L/S) as detected by an FDA-approved test, with a median treatment duration of 4.3 months (PMID: 29860938; NCT02074839). | detail... 29860938 detail... |
IDH1 R132C | chondrosarcoma | predicted - sensitive | IDH1 Inhibitor | Ivosidenib | Case Reports/Case Series | Actionable | In a Phase I trial, Tibsovo (ivosidenib) treatment was tolerated, substantially decreased plasma 2-HG levels, and resulted in a median progression-free survival of 5.6 months and stable disease in 52% (11/21) of patients with chondrosarcoma harboring IDH1 mutations, including IDH1 R132C (n=13) (PMID: 32208957; NCT02073994). | 32208957 |
IDH1 R132C | acute myeloid leukemia | sensitive | IDH1 Inhibitor | Azacitidine + Ivosidenib | Phase Ib/II | Actionable | In a Phase Ib trial, Tibsovo (ivosidenib) and Vidaza (azacitidine) combination treatment demonstrated a favorable safety profile and resulted in an objective response rate (ORR) of 78.3% (18/23, 14 complete remission) and a 12-month overall survival probability of 82% in patients with newly diagnosed acute myeloid leukemia harboring IDH1 R132C (n=14), R132H (n=4), or R132L (n=3) mutations (PMID: 33119479; NCT02677922). | 33119479 |
IDH1 R132C | acute myeloid leukemia | sensitive | IDH1 Inhibitor | Azacitidine + Ivosidenib | FDA approved - On Companion Diagnostic | Actionable | In a Phase III trial (AGILE) that supported FDA approval, Tibsovo (ivosidenib) and Vidaza (azacitidine) combination therapy significantly improved event-free survival (HR 0.33, p=0.002) and median overall survival (24.0 vs 7.9 mo, HR 0.44, p=0.001) compared to Vidaza (azacitidine) plus placebo in patients with newly diagnosed acute myeloid leukemia harboring IDH1 mutations including R132C/H/G/L/S (PMID: 35443108; NCT03173248). | 35443108 detail... detail... |
IDH1 R132C | intrahepatic cholangiocarcinoma | sensitive | Dasatinib | Preclinical | Actionable | In a preclinical study, Sprycel (dasatinib) inhibited growth of intrahepatic cholangiocarcinoma cells harboring IDH1 R132C in culture, and suppressed tumor growth in PDX models (PMID: 27231123). | 27231123 | |
IDH1 R132C | high grade glioma | sensitive | IDH1 Inhibitor | AGI-5198 | Preclinical | Actionable | In a preclinical study, AGI-5198 inhibited growth and promoted differentiation in glioma cells expressing IDH1 R132C (PMID: 23558169). | 23558169 |
IDH1 R132C | cholangiocarcinoma | predicted - sensitive | IDH1 Inhibitor | Ivosidenib | FDA approved - On Companion Diagnostic | Actionable | In a Phase III (ClarIDHy) trial that supported FDA approval, Tibsovo (ivosidenib) treatment significantly improved median progression-free survival (2.7 vs 1.4 mo, HR=0.37, p<0.001) and prolonged median overall survival (10.8 vs 9.7 mo, HR=0.69, p=0.06) compared to placebo in patients with advanced cholangiocarcinoma harboring IDH1 mutations including R132C/H/L/G/S, resulted in favorable objective response rate (2%, 3/124 vs 0%, 0/61) and stable disease rate (51% vs 28%) (PMID: 32416072; NCT02989857). | detail... detail... 32416072 |
IDH1 R132C | leukemia | sensitive | TETi76 | Preclinical - Cell culture | Actionable | In a preclinical study, TETi76 treatment decreased viability of a leukemia cell line expressing IDH1 R132C in culture (PMID: 33681816). | 33681816 | |
IDH1 R132C | acute myeloid leukemia | sensitive | IDH1 Inhibitor | BAY1436032 | Preclinical - Pdx & cell culture | Actionable | In a preclinical study, BAY1436032 decreased R-2HG levels and inhibited growth of primary acute myeloid leukemia (AML) cells harboring IDH1 R132C in culture, and decreased blast number and increased survival of two AML patient-derived xenograft (PDX) models, one which harbored additional alterations in FLT3, NPM1, and NRAS and one which harbored a KMT2A (MLL) alteration (PMID: 28232670). | 28232670 |
Clinical Trial | Phase | Therapies | Title | Recruitment Status | Covered Countries | Other Countries |
---|---|---|---|---|---|---|
NCT04164901 | Phase III | AG-881 | Study of Vorasidenib (AG-881) in Participants With Residual or Recurrent Grade 2 Glioma With an IDH1 or IDH2 Mutation (INDIGO) | Active, not recruiting | USA | ITA | FRA | ESP | DEU | CAN | 4 |
NCT03953898 | Phase II | Olaparib | Using the Anticancer Drug Olaparib to Treat Relapsed/Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome With an Isocitrate Dehydrogenase (IDH) Mutation | Recruiting | USA | 0 |
NCT04088188 | Phase I | Cisplatin + Gemcitabine + Pemigatinib Cisplatin + Gemcitabine + Ivosidenib | Gemcitabine and Cisplatin With Ivosidenib or Pemigatinib for the Treatment of Unresectable or Metastatic Cholangiocarcinoma | Recruiting | USA | 0 |
NCT04056910 | Phase II | Ivosidenib + Nivolumab | Ivosidenib (AG-120) With Nivolumab in IDH1 Mutant Tumors | Recruiting | USA | 0 |